小细胞肺癌（SCLC）是一种侵袭性疾病，预后不佳。在一线环境中将免疫检查点抑制剂添加到标准铂类化疗中只能在患者亚组中实现持久获益。因此，预测性生物标志物的鉴定是一项紧迫的未满足的医疗需求。通过基因表达谱和两个 9 色多重免疫荧光组对接受阿特珠单抗加卡铂-依托泊苷的初治广泛期 (ES) SCLC 患者的肿瘤样本进行分析，以表征免疫浸润和 SCLC 亚型。评估了组织生物标志物与治疗失败时间 (TTF)、无进展生存期 (PFS) 和总生存期 (OS) 的关联。纳入了 42 名患者。耗竭的 CD8 相关基因的较高表达与较长的 TTF 和 PFS 独立相关，而 B 淋巴细胞密度的增加与较长的 TTF 和 OS 相关。靠近肿瘤细胞的 M2 样巨噬细胞和靠近 CD4 T 淋巴细胞的 CD8 T 细胞比例较高，分别与 TF 风险增加和生存期延长相关。较低的 TF、疾病进展和死亡风险与较高密度的 ASCL1 肿瘤细胞相关，而 POU2F3 的表达与较短的生存期相关。综合评分结合耗尽的 CD8 相关基因的表达、B 淋巴细胞密度、ASCL1 肿瘤表达和靠近肿瘤细胞的 CD163 巨噬细胞的定量，能够将患者分为高风险组和低风险组。 总之，我们确定了组织生物标志物和综合评分可以预测 ES-SCLC 患者从化学免疫治疗中获得更高的益处。© 作者（或其雇主）2024。CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only in a patient subgroup. Thus, the identification of predictive biomarkers is an urgent unmet medical need.Tumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin-etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, to characterize the immune infiltrate and SCLC subtypes. Associations of tissue biomarkers with time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS), were assessed.42 patients were included. Higher expression of exhausted CD8-related genes was independently associated with a longer TTF and PFS while increased density of B lymphocytes correlated with longer TTF and OS. Higher percentage of M2-like macrophages close to tumor cells and of CD8+T cells close to CD4+T lymphocytes correlated with increased risk of TF and longer survival, respectively. A lower risk of TF, disease progression and death was associated with a higher density of ASCL1+tumor cells while the expression of POU2F3 correlated with a shorter survival. A composite score combining the expression of exhausted CD8-related genes, B lymphocyte density, ASCL1 tumor expression and quantification of CD163+macrophages close to tumor cells, was able to stratify patients into high-risk and low-risk groups.In conclusion, we identified tissue biomarkers and a combined score that can predict a higher benefit from chemoimmunotherapy in ES-SCLC patients.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.